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Review
. 2020 Aug 27;22(9):69.
doi: 10.1007/s11906-020-01067-9.

ENaC in Salt-Sensitive Hypertension: Kidney and Beyond

Ashley L Pitzer  1 , Justin P Van Beusecum  1 , Thomas R Kleyman  2 , Annet Kirabo  3   4
Affiliations
Review

ENaC in Salt-Sensitive Hypertension: Kidney and Beyond

Ashley L Pitzer et al. Curr Hypertens Rep. .

Abstract

Purpose of review: The main goal of this article is to discuss the role of the epithelial sodium channel (ENaC) in extracellular fluid and blood pressure regulation.

Recent findings: Besides its role in sodium handling in the kidney, recent studies have found that ENaC expressed in other cells including immune cells can influence blood pressure via extra-renal mechanisms. Dendritic cells (DCs) are activated and contribute to salt-sensitive hypertension in an ENaC-dependent manner. We discuss recent studies on how ENaC is regulated in both the kidney and other sites including the vascular smooth muscles, endothelial cells, and immune cells. We also discuss how this extra-renal ENaC can play a role in salt-sensitive hypertension and its promise as a novel therapeutic target. The role of ENaC in blood pressure regulation in the kidney has been well studied. Recent human gene sequencing efforts have identified thousands of variants among the genes encoding ENaC, and research efforts to determine if these variants and their expression in extra-renal tissue play a role in hypertension will advance our understanding of the pathogenesis of ENaC-mediated cardiovascular disease and lead to novel therapeutic targets.

Keywords: ENaC; Hypertension; Inflammation; Sodium.

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Conflict of interest statement

The authors declare no conflicts of interest relevant to this manuscript.

Figures

Fig. 1
Fig. 1
ENaC regulation in the kidney, vasculature, and immune system. ENaC expression and activation in renal distal tubule epithelial cells is regulated by hormonal factors, proteases, lipids, and select ions promoting hypertension, renal injury and inflammation, hypokalemia, and metabolic alkalosis. In vasculature, inhibition of ENaC leads to increased nitric oxide production mediating vascular tone and myogenic response. Activation of ENaC in innate immune cells stimulates ROS production, pro-inflammatory cytokine secretion, and antigen presentation resulting in inflammation and salt-sensitive hypertension
See this image and copyright information in PMC

References

    1. Muntner P, Carey RM, Gidding S, Jones DW, Taler SJ, Wright JT, Jr, Whelton PK. Potential US population impact of the 2017 ACC/AHA High Blood Pressure Guideline. Circulation. 2018;137(2):109–118. - PMC - PubMed
    1. Whelton PK, He J. Health effects of sodium and potassium in humans. Curr Opin Lipidol. 2014;25(1):75–79. - PubMed
    1. Weinberger MH, Miller JZ, Luft FC, Grim CE, Fineberg NS. Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension. 1986;8(6 Pt 2):II127–II134. - PubMed
    1. Morimoto A, Uzu T, Fujii T, Nishimura M, Kuroda S, Nakamura S, Inenaga T, Kimura G. Sodium sensitivity and cardiovascular events in patients with essential hypertension. Lancet. 1997;350(9093):1734–1737. - PubMed
    1. Weinberger MH, Fineberg NS, Fineberg SE, Weinberger M. Salt sensitivity, pulse pressure, and death in normal and hypertensive humans. Hypertension. 2001;37(2 Pt 2):429–432. - PubMed

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